In vivo phenotypic screening: clinical proof of concept for a drug repositioning approach.

Abstract

In vivo phenotypic screening and drug repositioning are strategies developed as alternatives to underperforming hypothesis-driven molecular target based drug discovery efforts. This article reviews examples of drugs identified by phenotypic observations and describes the use of the theraTRACE®in vivo screening platform for finding and developing new indications for discontinued clinical compounds. Clinical proof-of-concept for the platform is exemplified by MLR-1023, a repositioned compound that has recently shown significant clinical efficacy in Type 2 diabetes patients. These findings validate an in vivo screening approach for drug development and underscore the importance of alternatives to target and mechanism based strategies that have failed to produce adequate numbers of new medicines.

• Authors: John R Ciallella, Andrew G Reaume
• Journal: Drug discovery today. Technologies (Drug Discov Today Technol) Vol. 23 Pg. 45-52 (Mar 2017) ISSN: 1740-6749 [Electronic] England
• PMID: 28647085 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Pyrimidinones
• 5-(3-methylphenoxy)-2(1H)-pyrimidinone

Topics

• Diabetes Mellitus, Type 2 (drug therapy)
• Drug Discovery
• Drug Evaluation, Preclinical
• High-Throughput Screening Assays
• Humans
• Pyrimidinones (therapeutic use)